Fructose overconsumption-induced reprogramming of microglia metabolism and function.

The overconsumption of dietary fructose has been proposed as a major culprit for the rise of many metabolic diseases in recent years, yet the relationship between a high fructose diet and neurological dysfunction remains to be explored. Although fructose metabolism mainly takes place in the liver and intestine, recent studies have shown that a hyperglycemic condition could induce fructose metabolism in the brain. Notably, microglia, which are tissue-resident macrophages (Mφs) that confer innate immunity in the brain, also express fructose transporters (GLUT5) and are capable of utilizing fructose as a carbon fuel. Together, these studies suggest the possibility that a high fructose diet can regulate the activation and inflammatory response of microglia by metabolic reprogramming, thereby altering the susceptibility of developing neurological dysfunction. In this review, the recent advances in the understanding of microglia metabolism and how it supports its functions will be summarized. The results from both in vivo and in vitro studies that have investigated the mechanistic link between fructose-induced metabolic reprogramming of microglia and its function will then be reviewed. Finally, areas of controversies and their associated implications, as well as directions that warrant future research will be highlighted.

Understanding the role of the fructose-1,6-bisphosphatase gene for enhancing the photosynthetic rate in Arabidopsis thaliana.

Transgenic Arabidopsis thaliana (ecotype Columbia) was successfully transformed with the gene fructose-1,6-bisphosphatase (FBPas e) and named as AtFBPase plants. Transgenic plants exhibited stable transformation, integration and significantly higher expressions for the transformed gene. Morphological evaluation of transgenic plants showed increased plant height (35cm), number of leaves (25), chlorophyll contents (28%), water use efficiency (increased from 1.5 to 2.6µmol CO2 µmol-1 H2 O) and stomatal conductance (20%), which all resulted in an enhanced photosynthetic rate (2.7µmolm-2 s-1 ) compared to wild type plants. This study suggests the vital role of FBPase gene in the modification of regulatory pathways to enhance the photosynthetic rate, which can also be utilised for economic crops in future.

Enhancement of the d-Allulose 3-Epimerase Expression in Bacillus subtilis through Both Transcriptional and Translational Regulations.

d-Allulose, a functional bulk sweetener, has recently attracted increasing attention because of its low-caloric-ness properties and diverse health effects. d-Allulose is industrially produced by the enzymatic epimerization of d-fructose, which is catalyzed by ketose 3-epimerase (KEase). In this study, the food-grade expression of KEase was studied using Bacillus subtills as the host. Clostridium sp. d-allulose 3-epimerase (Clsp-DAEase) was screened from nine d-allulose-producing KEases, showing better potential for expression in B. subtills WB600. Promoter-based transcriptional regulation and N-terminal coding sequence (NCS)-based translational regulation were studied to enhance the DAEase expression level. In addition, the synergistic effect of promoter and NCS on the Clsp-DAEase expression was studied. Finally, the strain with the combination of a PHapII promoter and gln A-Up NCS was selected as the best Clsp-DAEase-producing strain. It efficiently produced Clsp-DAEase with a total activity of 333.2 and 1860.6 U/mL by shake-flask and fed-batch cultivations, respectively.

Inflammatory response in dairy cows caused by heat stress and biological mechanisms for maintaining homeostasis.

Climate change increases global temperatures, which is lethal to both livestock and humans. Heat stress is known as one of the various livestock stresses, and dairy cows react sensitively to high-temperature stress. We aimed to better understand the effects of heat stress on the health of dairy cows and observing biological changes. Individual cows were divided into normal (21-22 °C, 50-60% humidity) and high temperature (31-32 °C, 80-95% humidity), respectively, for 7-days. We performed metabolomic and transcriptome analyses of the blood and gut microbiomes of feces. In the high-temperature group, nine metabolites including linoleic acid and fructose were downregulated, and 154 upregulated and 72 downregulated DEGs (Differentially Expressed Genes) were identified, and eighteen microbes including Intestinimonas and Pseudoflavonifractor in genus level were significantly different from normal group. Linoleic acid and fructose have confirmed that associated with various stresses, and functional analysis of DEG and microorganisms showing significant differences confirmed that high-temperature stress is related to the inflammatory response, immune system, cellular energy mechanism, and microbial butyrate production. These biological changes were likely to withstand high-temperature stress. Immune and inflammatory responses are known to be induced by heat stress, which has been identified to maintain homeostasis through modulation at metabolome, transcriptome and microbiome levels. In these findings, heat stress condition can trigger alteration of immune system and cellular energy metabolism, which is shown as reduced metabolites, pathway enrichment and differential microbes. As results of this study did not include direct phenotypic data, we believe that additional validation is required in the future. In conclusion, high-temperature stress contributed to the reduction of metabolites, changes in gene expression patterns and composition of gut microbiota, which are thought to support dairy cows in withstanding high-temperature stress via modulating immune-related genes, and cellular energy metabolism to maintain homeostasis.

Glycomacropeptide as an Efficient Agent to Fight Pathophysiological Mechanisms of Metabolic Syndrome.

There is currently a growing interest in the use of nutraceuticals as a means of preventing the development of complex diseases. Given the considerable health potential of milk-derived peptides, the aim of this study was to investigate the protective effects of glycomacropeptide (GMP) on metabolic syndrome. Particular emphasis was placed on the potential mechanisms mitigating cardiometabolic disorders in high-fat, high-fructose diet-fed mice in the presence of GMP or Bipro, an isocaloric control. The administration of GMP for 12 weeks reduced obesity, hyperglycemia and hyperinsulinemia caused by a high-fat, high-fructose diet, resulting in a decline in insulin resistance. GMP also lessened systemic inflammation, as indicated by decreased circulating inflammatory cytokines. In the intestinal and hepatic tissues, GMP improved homeostasis by increasing insulin sensitivity and attenuating high-fat, high-fructose-induced inflammation, oxidative stress and endoplasmic reticulum stress. Biochemical and histological analyses revealed improved hepatic steatosis and fatty acid composition in the livers of high-fat, high-fructose diet-fed mice treated with GMP compared to Bipro. A trend toward a decrease in bile acids without any marked changes in intestinal microbiota composition characterized GMP-treated animals compared to those administered Bipro. GMP offers considerable potential for fighting metabolic syndrome-related components and complications given its beneficial effects on risk factors such as inflammation, oxidative stress and endoplasmic reticulum stress without involving the intestinal microbiota.

Enhancing enzyme immobilization: Fabrication of biosilica-based organic-inorganic composite carriers for efficient covalent binding of D-allulose 3-epimerase.

D-allulose, an ideal low-calorie sweetener, is primarily produced through the isomerization of d-fructose using D-allulose 3-epimerase (DAE; EC 5.1.3.30). Addressing the gap in available immobilized DAE enzymes for scalable commercial D-allulose production, three core-shell structured organic-inorganic composite silica-based carriers were designed for efficient covalent immobilization of DAE. Natural inorganic diatomite was used as the core, while 3-aminopropyltriethoxysilane (APTES), polyethyleneimine (PEI), and chitosan organic layers were coated as the shells, respectively. These tailored carriers successfully formed robust covalent bonds with DAE enzyme conjugates, cross-linked via glutaraldehyde, and demonstrated enzyme activities of 372 U/g, 1198 U/g, and 381 U/g, respectively. These immobilized enzymes exhibited an expanded pH tolerance and improved thermal stability compared to free DAE. Particularly, the modified diatomite with PEI exhibited a higher density of binding sites than the other carriers and the PEI-coated immobilized DAE enzyme retained 70.4 % of its relative enzyme activity after ten cycles of reuse. This study provides a promising method for DAE immobilization, underscoring the potential of using biosilica-based organic-inorganic composite carriers for the development of robust enzyme systems, thereby advancing the production of value-added food ingredients like D-allulose.

Rootstock vigor dictates the canopy light environment that regulates metabolite profile and internal fruit quality development in peach.

Five rootstock cultivars of differing vigor: vigorous ('Atlas™' and 'Bright's Hybrid® 5'), standard ('Krymsk® 86' and 'Lovell') and dwarfing ('Krymsk® 1') grafted with 'Redhaven' as the scion were studied for their impact on productivity, mid-canopy photosynthetic active radiation transmission (i.e., light availability) and internal fruit quality. Αverage yield (kg per tree) and fruit count increased significantly with increasing vigor (trunk cross sectional area, TCSA). Α detailed peach fruit quality analysis on fruit of equal maturity (based on the index of absorbance difference, IAD) coming from trees with equal crop load (no. of fruit cm-2 of TCSA) characterized the direct impact of rootstock vigor on peach internal quality [dry matter content (DMC) and soluble solids concentration (SSC)]. DMC and SSC increased significantly with decreasing vigor and increasing light availability, potentially due to reduced intra-tree shading and better light distribution within the canopy. Physiologically characterized peach fruit mesocarp was further analyzed by non-targeted metabolite profiling using gas chromatography mass spectrometry (GC-MS). Metabolite distribution was associated with rootstock vigor class, mid-canopy light availability and fruit quality characteristics. Fructose, glucose, sorbose, neochlorogenic and quinic acids, catechin and sorbitol were associated with high light environments and enhanced quality traits, while sucrose, butanoic and malic acids related to low light conditions and inferior fruit quality. These outcomes show that while rootstock genotype and vigor are influencing peach tree productivity and yield, their effect on manipulating the light environment within the canopy also plays a significant role in fruit quality development.

Liver ChREBP deficiency inhibits fructose-induced insulin resistance in pregnant mice and female offspring.

High fructose intake during pregnancy increases insulin resistance (IR) and gestational diabetes mellitus (GDM) risk. IR during pregnancy primarily results from elevated hormone levels. We aim to determine the role of liver carbohydrate response element binding protein (ChREBP) in insulin sensitivity and lipid metabolism in pregnant mice and their offspring. Pregnant C57BL/6J wild-type mice and hepatocyte-specific ChREBP-deficient mice were fed with a high-fructose diet (HFrD) or normal chow diet (NC) pre-delivery. We found that the combination of HFrD with pregnancy excessively activates hepatic ChREBP, stimulating progesterone synthesis by increasing MTTP expression, which exacerbates IR. Increased progesterone levels upregulated hepatic ChREBP via the progesterone-PPARγ axis. Placental progesterone activated the progesterone-ChREBP loop in female offspring, contributing to IR and lipid accumulation. In normal dietary conditions, hepatic ChREBP modestly affected progesterone production and influenced IR during pregnancy. Our findings reveal the role of hepatic ChREBP in regulating insulin sensitivity and lipid homeostasis in both pregnant mice consuming an HFrD and female offspring, and suggest it as a potential target for managing gestational metabolic disorders, including GDM.

Profiling Cell Heterogeneity and Fructose Transporter Expression in the Rat Nephron by Integrating Single-Cell and Microdissected Tubule Segment Transcriptomes.

Single-cell RNA sequencing (scRNAseq) is a crucial tool in kidney research. These technologies cluster cells based on transcriptome similarity, irrespective of the anatomical location and order within the nephron. Thus, a transcriptome cluster may obscure the heterogeneity of the cell population within a nephron segment. Elevated dietary fructose leads to salt-sensitive hypertension, in part, through fructose reabsorption in the proximal tubule (PT). However, the organization of the four known fructose transporters in apical PTs (SGLT4, SGLT5, GLUT5, and NaGLT1) remains poorly understood. We hypothesized that cells within each subsegment of the proximal tubule exhibit complex, heterogeneous fructose transporter expression patterns. To test this hypothesis, we analyzed rat kidney transcriptomes and proteomes from publicly available scRNAseq and tubule microdissection databases. We found that microdissected PT-S1 segments consist of 81% ± 12% cells with scRNAseq-derived transcriptional characteristics of S1, whereas PT-S2 express a mixture of 18% ± 9% S1, 58% ± 8% S2, and 19% ± 5% S3 transcripts, and PT-S3 consists of 75% ± 9% S3 transcripts. The expression of all four fructose transporters was detectable in all three PT segments, but key fructose transporters SGLT5 and GLUT5 progressively increased from S1 to S3, and both were significantly upregulated in S3 vs. S1/S2 (Slc5a10: 1.9 log2FC, p < 1 × 10-299; Scl2a5: 1.4 log2FC, p < 4 × 10-105). A similar distribution was found in human kidneys. These data suggest that S3 is the primary site of fructose reabsorption in both humans and rats. Finally, because of the multiple scRNAseq transcriptional phenotypes found in each segment, our findings also imply that anatomical labels applied to scRNAseq clusters may be misleading.

A multi-modal approach to investigate Desmodium gangeticum's influence on stress-induced male infertility: In vivo, in vitro, and in silico assessments.

Physical and psychological stress has an inverse relation with male libido and sperm quality. The present study investigates the potential fertility-enhancing properties of Desmodium gangeticum (DG) root extracts in male Wister rats subjected to immobilization-induced stress (SIMB). DG roots were extracted using n-hexane (HEDG), chloroform (CEDG), and water (AEDG). In the pilot study, aphrodisiac protentional was investigated at two doses (125 and 250 mg kg-1) of each extract. In the main study, the HEDG and AEDG at 125 and 250 mg kg-1 were challenged for the stress by immobilization (SIMB), for 6 h daily over 28 days. Parameters assessed included aphrodisiac effects, gonadosomatic index (GSI), semen quality, sperm quantity, fructose content, serum hormonal levels, testicular oxidative stress, and testicular histopathology. Additional in silico studies, including the lipid solubility index, molecular docking, molecular dynamics, and SymMap studies were conducted for validation. HEDG demonstrated significant aphrodisiac activity, improved - GSI, sperm quality and quantity, and fructose content, serum testosterone levels, histological changes induced by SIMB in the testes. Swiss ADME studies indicated Gangetin (a pterocarpan) had a high brain permeation index (4.81), a superior docking score (-8.22), and higher glide energy (-42.60), compared with tadalafil (-7.17). The 'Lig fit Prot' plot in molecular dynamics simulations revealed a strong alignment between Gangetin and phosphodiesterase type 5 (PDE5). HEDG exerts aphrodisiac effects by increasing blood testosterone levels and affecting PDE5 activity. The protective effects on spermatozoa-related parameters and testicular histological changes are attributed to the antioxidant and anti-inflammatory properties, of pterocarpan (gangetin).

Variation of sugar compounds in Phoebe chekiangensis seeds during natural desiccation.

To investigate the role of sugar metabolism in desiccation-sensitive seeds, we performed a natural desiccation treatment on Phoebe chekiangensis seeds in a room and systematically analyzed the changes in seed germination, sugar compounds, malondialdehyde, and relative electrical conductivity during the seed desiccation. The results revealed that the initial moisture content of P. chekiangensis seed was very high (37.06%) and the seed was sensitive to desiccation, the germination percentage of the seed decreased to 5.33% when the seed was desiccated to 22.04% of moisture content, therefore, the seeds were considered recalcitrant. Based on the logistic model, we know that the moisture content of the seeds is 29.05% when the germination percentage drops to 50% and that it is desirable to keep the seed moisture content above 31.74% during ambient transportation. During seed desiccation, sucrose and trehalose contents exhibited increasing trends, and raffinose also increased during the late stage of desiccation, however, low levels of the non-reducing sugar accumulations may not prevent the loss of seed viability caused by desiccation. Glucose and fructose predominated among sugar compounds, and they showed a slight increase followed by a significant decrease. Their depletion may have contributed to the accumulation of sucrose and raffinose family oligosaccharides. Correlation analysis revealed a significant relationship between the accumulation of sucrose, trehalose, and soluble sugars, and the reduction in seed viability. Sucrose showed a significant negative correlation with glucose and fructose. Trehalose also exhibited the same pattern of correlation. These results provided additional data and theoretical support for understanding the mechanism of sugar metabolism in seed desiccation sensitivity.

Development of a tamarind-based functional beverage with partially-hydrolyzed agave syrup and the health effects of its consumption in C57BL/6 mice.

Excess consumption of sweetened beverages is associated with a global rise in metabolic diseases. Tamarind and partially-hydrolyzed agave syrup have potential for developing healthier beverages. Our objective was to develop a functional beverage using these ingredients (PH-AS-B). We also evaluate shelf-life stability (physicochemical, microbiological, and antioxidant properties) and health effects in C57BL/6 mice compared with tamarind beverages sweetened with glucose or fructose. Optimal tamarind extraction conditions were a 1:10 ratio (g pulp/mL water) and boiling for 30 min, and the resulting beverage had a shelf life of two months at 4 °C. Non-volatile metabolites were identified using HPLC/MS. PH-AS-B was associated with decreased blood cholesterol (5%) and triglyceride (20-35%) concentrations in healthy mice as well as lower lipid (82%) concentrations and evidence of protein oxidation (42%) in the liver, compared with glucose- and fructose-sweetened tamarind beverages. In conclusion, PH-AS-B was stable and associated with beneficial metabolic properties in healthy mice.

6-Gingerol alleviates ectopic lipid deposition in skeletal muscle by regulating CD36 translocation and mitochondrial function.

Ectopic lipid deposition (ELD) and mitochondrial dysfunction are common causes of metabolic disorders in humans. Consuming too much fructose can result in mitochondrial dysfunction and metabolic disorders. 6-Gingerol, the main component of ginger (Zingiber officinale Roscoe), has been proven to alleviate metabolic disorders. This study seeks to examine the effects of 6-gingerol on metabolic disorders caused by fructose and uncover the underlying molecular mechanisms. In this study, the results showed that 6-Gingerol ameliorated high-fructose-induced metabolic disorders. Moreover, it inhibited CD36 membrane translocation, increased CD36 expression in the mitochondria, and decreased the O-GlcNAc modification of CD36 and OGT expression in vitro and vivo. In addition, 6-Gingerol enhanced the performance of mitochondria in the skeletal muscle and boosted the respiratory capability of L6 myotubes. This study provides a theoretical basis and new insights for the development of lipid-lowering drugs in clinical practice.

Economical one-pot synthesis of isoquercetin and D-allulose from quercetin and sucrose using whole-cell biocatalyst.

Isoquercetin and D-allulose have diverse applications and significant value in antioxidant, antibacterial, antiviral, and lipid metabolism. Isoquercetin can be synthesized from quercetin, while D-allulose is converted from D-fructose. However, their production scale and overall quality are relatively low, leading to high production costs. In this study, we have devised a cost-effective one-pot method for biosynthesizing isoquercetin and D-allulose using a whole-cell biocatalyst derived from quercetin and sucrose. To achieve this, the optimized isoquercetin synthase and D-allulose-3-epimerase were initially identified through isofunctional gene screening. In order to reduce the cost of uridine diphosphate glucose (UDPG) during isoquercetin synthesis and ensure a continuous supply of UDPG, sucrose synthase is introduced to enable the self-circulation of UDPG. At the same time, the inclusion of sucrose permease was utilized to successfully facilitate the catalytic production of D-allulose in whole cells. Finally, the recombinant strain BL21/UGT-SUS+DAE-SUP, which overexpresses MiF3GTMUT, GmSUS, EcSUP, and DAEase, was obtained. This strain co-produced 41±2.4 mg/L of isoquercetin and 5.7±0.8 g/L of D-allulose using 120 mg/L of quercetin and 20 g/L of sucrose as substrates for 5 h after optimization. This is the first green synthesis method that can simultaneously produce flavonoid compounds and rare sugars. These findings provide valuable insights and potential for future industrial production, as well as practical applications in factories.

Fructose regulates the pentose phosphate pathway and induces an inflammatory and resolution phenotype in Kupffer cells.

Over-consumption of fructose in adults and children has been linked to increased risk of non-alcoholic fatty liver disease (NAFLD). Recent studies have highlighted the effect of fructose on liver inflammation, fibrosis, and immune cell activation. However, little work summarizes the direct impact of fructose on macrophage infiltration, phenotype, and function within the liver. We demonstrate that chronic fructose diet decreased Kupffer cell populations while increasing transitioning monocytes. In addition, fructose increased fibrotic gene expression of collagen 1 alpha 1 (Col1a1) and tissue metallopeptidase inhibitor 1 (Timp1) as well as inflammatory gene expression of tumor necrosis factor alpha (Tnfa) and expression of transmembrane glycoprotein NMB (Gpnmb) in liver tissue compared to glucose and control diets. Single cell RNA sequencing (scRNAseq) revealed fructose elevated expression of matrix metallopeptidase 12 (Mmp12), interleukin 1 receptor antagonist (Il1rn), and radical S-adenosyl methionine domain (Rsad2) in liver and hepatic macrophages. In vitro studies using IMKC and J774.1 cells demonstrated decreased viability when exposed to fructose. Additionally, fructose increased Gpnmb, Tnfa, Mmp12, Il1rn, and Rsad2 in unpolarized IMKC. By mass spectrometry, C13 fructose tracing detected fructose metabolites in glycolysis and the pentose phosphate pathway (PPP). Inhibition of the PPP further increased fructose induced Il6, Gpnmb, Mmp12, Il1rn, and Rsad2 in nonpolarized IMKC. Taken together, fructose decreases cell viability while upregulating resolution and anti-inflammatory associated genes in Kupffer cells.

Ingestion of Bean Leaves Reduces Metabolic Complications and Restores Intestinal Integrity in C57BL/6 Mice with Obesity Induced by a High-Fat and High-Fructose Diet.

Consumption of foods with fiber and compounds can promote gastrointestinal health and reduce obesity complications. Therefore, treatment with common bean leaves (BL) against obesity was evaluated in mice with a high-fat and high-fructose diet (HFFD) for 14 weeks. The bromatological and phytochemical characterization of BL were determined. Afterwards, the animals were supplemented with BL (10%) or a standard diet (SD) as a strategy to encourage a healthy diet for 12 additional weeks. Changes in body composition, lipid profile, and intestinal integrity were analyzed. The characterization of BL stood out for its content of 27.2% dietary fiber, total phenolics (475.04 mg/100 g), and saponins (2.2 mg/100 g). The visceral adipose tissue (VAT) decreased in the BL group by 52% compared to the HFFD group. Additionally, triglyceride levels were 23% lower in the BL consumption group compared to the HFFD group. The improvement in lipid profile was attributed to the 1.77-fold higher fecal lipid excretion in the BL consumption group compared to the HFFD group and the inhibition of pancreatic lipase by 29%. Furthermore, BL supplementation reduced the serum levels of IL-6 (4.4-fold) and FITC-dextran by 50% compared with those in the HFFD group. Metabolic endotoxemia was inhibited after BL supplementation (-33%) compared to the HFFD group. BL consumption as a treatment in obese mice reduces adipose tissue accumulation and improves the lipid profile. Furthermore, we report for the first time that BL consumption improves intestinal integrity.

Physiological and molecular changes of onion (Allium cepa L.) seeds under different aging conditions.

BACKGROUND: Onion seeds have limited storage capacity compared to other vegetable seeds. It is crucial to identify the mechanisms that induce tolerance to storage conditions and reduce seed deterioration. To address this goal, an experiment was conducted to evaluate changes in germination, biochemical, physiological, and molecular characteristics of onion seed landraces (Horand, Kazerun landraces and Zargan cultivar) at different aging levels (control, three-days and six-days accelerated aging, and natural aging for one year). RESULTS: The findings suggest that there was an increase in glucose, fructose, total sugar, and electrolyte leakage in the Horand (HOR), Kazerun (KAZ) landraces, and Zarghan (ZAR) cultivar, with Kazerun exhibiting the greatest increase. The percentage and rate of germination of Kazerun decreased by 54% and 33%, respectively, in six-day accelerated aging compared to the control, while it decreased by 12% and 14%, respectively, in Horand. Protein content decreased with increasing levels of aging, with a decrease of 26% in Kazerun landrace at six days of aging, while it was 16% in Horand landrace. The antioxidant activities of catalase, superoxide dismutase, and glutathione peroxidase decreased more intensively in Kazerun. The expression of AMY1, BMY1, CTR1, and NPR1 genes were lower in Kazerun landraces than in Horand and Zargan at different aging levels. CONCLUSIONS: The AMY1, BMY1, CTR1, and NPR1 genes play a pivotal role in onion seed germination, and their downregulation under stressful conditions has been shown to decrease germination rates. In addition, the activity of CAT, SOD, and GPx enzymes decreased by seed aging, and the amount of glucose, fructose, total sugar and electrolyte leakage increased, which ultimately led to seed deterioration. Based on the results of this experiment, it is recommended to conduct further studies into the molecular aspects involved in onion seed deterioration. More research on the genes related to this process is suggested, as well as investigating the impact of different priming treatments on the genes expression involved in the onion seed aging process.

Widely targeted quantitative lipidomics reveal lipid remodeling in adipose tissue after long term of the combined exposure to bisphenol A and fructose.

Adipose tissue is the main organ that stores lipids and it plays important roles in metabolic balance in the body. We recently reported in Human and Experimental Toxicology that the combined exposure to BPA and fructose may interfere with energy metabolism of adipose tissue. However, it is still unclear whether the combined exposure to BPA and fructose has the possibility to induce lipid remodeling in adipose tissue. In the present study, we performed a widely targeted quantitative lipidomic analysis of the adipose tissue of rats after 6 months of BPA and fructose combined exposure. We totally determined 734 lipid molecules in the adipose tissue of rats. Principal component analysis (PCA) showed the group of the combined exposure to higher-dose (25 µg/kg every other day) BPA and fructose can be distinguished from the groups of control, higher-dose BPA exposure and fructose exposure clearly. Partial least squares-discriminant analysis (PLS-DA) and univariate statistical analysis displayed lipids of PC(18:0_ 20:3), TG(8:0_14:0_16:0), TG(12:0_14:0_16:1), TG(10:0_16:0_16:1), TG(12:0_ 14:0_18:1), TG(14:0_ 16:0_16:1), TG(14:0_14:1_16:1), TG(8:0_ 16:1_16:2), TG(14:1_16:1_ 16:1), TG(16:1_18:1_18:1), TG(16:0_16:1_20:4) and TG(15:0_18:1_ 24:1) may contributed the most to the discrimination. These findings indicated that combined exposure to BPA and fructose has the potential to cause lipid remodeling in adipose tissue.

Growth-Coupled Evolutionary Pressure Improving Epimerases for D-Allulose Biosynthesis Using a Biosensor-Assisted In Vivo Selection Platform.

Fast screening strategies that enable high-throughput evaluation and identification of desired variants from diversified enzyme libraries are crucial to tailoring biocatalysts for the synthesis of D-allulose, which is currently limited by the poor catalytic performance of ketose 3-epimerases (KEases). Here, the study designs a minimally equipment-dependent, high-throughput, and growth-coupled in vivo screening platform founded on a redesigned D-allulose-dependent biosensor system. The genetic elements modulating regulator PsiR expression levels undergo systematic optimization to improve the growth-responsive dynamic range of the biosensor, which presents ≈30-fold facilitated growth optical density with a high signal-to-noise ratio (1.52 to 0.05) toward D-allulose concentrations from 0 to 100 mm. Structural analysis and evolutionary conservation analysis of Agrobacterium sp. SUL3 D-allulose 3-epimerase (ADAE) reveal a highly conserved catalytic active site and variable hydrophobic pocket, which together regulate substrate recognition. Structure-guided rational design and directed evolution are implemented using the growth-coupled in vivo screening platform to reprogram ADAE, in which a mutant M42 (P38N/V102A/Y201L/S207N/I251R) is identified with a 6.28-fold enhancement of catalytic activity and significantly improved thermostability with a 2.5-fold increase of the half-life at 60 °C. The research demonstrates that biosensor-assisted growth-coupled evolutionary pressure combined with structure-guided rational design provides a universal route for engineering KEases.

Consumo de fructosa y síndrome metabólico en pacientes adultos de un Hospital Militar / Fructose consumption and metabolic syndrome in adult patients of a military hospital

Introducción: La fructosa de la dieta se metaboliza a nivel hepático, en donde estimula la fructólisis, la glucólisis, la lipogénesis y la producción de glucosa, esto conlleva a la dislipidemia mixta, hiperglucemia e hígado graso; aumentando el riesgo de síndrome metabólico.Objetivo: Determinar la asociación entre el consumo de fructosa y síndrome metabólico en pacientes adultos atendidos en el Hospital Militar Central “Coronel Luis Arias Schreiber”.Materiales y Métodos: Investigación de enfoque cuantitativo, diseño no experimental, transversal, correlacional-causal. La población de estudio estuvo conformada por 75 pacientes adultos. Se incluyó pacientes mayores de 18 años de edad; quienes en forma voluntaria firmaron el consentimiento informado y presentaron registros actualizados de perfil bioquímico, fueron excluidos pacientes con discapacidad mental, motora y/o física. Los valores de presión arterial y perfil bioquímico; se obtuvo de las historias clínicas y la valoración antropométrica a través de la medición del peso corporal, talla y circunferencia abdominal; la ingesta de fructosa se obtuvo a través de un cuestionario de frecuencia de consumo semicuantitativo. Se utilizó la prueba estadística de Chi cuadrado para evaluar la asociación de variables.Resultados: El 61,3% presentó Síndrome Metabólico (SM), el 88% presentan un inadecuado consumo de fructosa (>25g/día). El índice de masa corporal (IMC) promedio fue de 30,34 (DE ±4,0); el nivel de glucosa en ayunas fue 100,13 mg/dL (DE ±11,25). Al asociar el consumo inadecuado de fructosa con el Síndrome Metabólico, se obtuvo un valor p= 0,010 (p<0,05). Asimismo, el consumo inadecuado de fructosa añadida tuvo asociación con el SM (p<0,05). No obstante, al asociar ingesta de fructosa natural con el SM, se obtuvo p =0.466 (p>0,05).(AU)

Introduction: Dietary fructose is metabolized in the liver,where it stimulates fructolysis, glycolysis, lipogenesis andglucose production, which leads to mixed dyslipidemia, hy-perglycemia and fatty liver; increasing the risk of metabolicsyndrome. Objetive: Determine the association between fructose con-sumption and metabolic syndrome in adult patients treated atthe “Coronel Luis Arias Schreiber” Central Military Hospital. Materials and methods: A quantitative approach studywas carried out, with a non-experimental, cross-sectional andcorrelational-causal design. The study population consisted of 75 adult patients. Patients over 18 years of age were in-cluded; who voluntarily signed the informed consent and pre-sented updated biochemical profile records. Patients withmental, motor and/or physical disabilities were excluded.Blood pressure and biochemical profile values were obtainedfrom medical records and anthropometric assessmentthrough measurement of body weight, height, and abdominalcircumference. Fructose intake was obtained through a semi-quantitative consumption frequency questionnaire. The Chisquare statistical test was used to evaluate the association ofvariables. Results: 61.3% presented Metabolic Syndrome (MS), 88%presented inadequate fructose consumption (>25g/day). Theaverage body mass index (BMI) was 30.34 (SD ±4.0); Thefasting glucose level was 100.13 mg/dL (SD ±11.25). Whenassociating inadequate fructose consumption with MetabolicSyndrome, a p value = 0.010 (p < 0.05) was obtained.Likewise, inadequate consumption of added fructose was as-sociated with MS (p<0.05). However, when associating natu-ral fructose intake with MS, p =0.466 (p>0.05) was obtained.Conclusions. A high consumption of added fructose in in-dustrialized foods has a greater association with the develop-ment of Metabolic Syndrome; It is necessary to reduce thefructose content in industrialized foods.(AU)